Kolarič A, Švajger U, Tomašič T, Brox R, Frank T, Minovski N, Tschammer N, Anderluh M (2018)
Publication Type: Journal article
Publication year: 2018
Book Volume: 154
Pages Range: 68-90
DOI: 10.1016/j.ejmech.2018.05.013
Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation. Para-methoxy substitution leads to functional antagonism, while para-chloro triggers agonism. Additionally, we discovered that chemotaxis is not completely correlated with G protein pathways. This is the first work in which we have on a series of compounds successfully demonstrated that it is possible to produce selective as well as dual-acting modulators of chemokine receptors, which is very promising for future research in the field of discovery of selective or dual modulators of chemokine receptors.
APA:
Kolarič, A., Švajger, U., Tomašič, T., Brox, R., Frank, T., Minovski, N.,... Anderluh, M. (2018). Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators. European Journal of Medicinal Chemistry, 154, 68-90. https://dx.doi.org/10.1016/j.ejmech.2018.05.013
MLA:
Kolarič, Anja, et al. "Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators." European Journal of Medicinal Chemistry 154 (2018): 68-90.
BibTeX: Download